Radioenhancement by cisplatin with accelerated fractionated radiotherapy in a human tumour xenograft

The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tumours were exposed to twice-daily 2-Gy fractions, applied 6 h apart over 2 weeks, 5 days a week, alone or combined with cisplatin given at maximally tolerated doses in three different schedules: (1) i.p. as a single bolus (SB) or (2) i.p. as a daily bolus at 30 min before the first daily radiation fraction or (3) s.c. as a continuous infusion through a mini-osmotic pump over 13 days, commencing 24 h prior to the first daily radiation fraction. The end point for the study was tumour growth delay (TGD), calculated as the difference between the delay in regrowth to 200% of the initial tumour size in treated versus control mice. SB cisplatin plus radiation showed only an additive effect on TGD, whereas daily-bolus and continuous-infusion cisplatin demonstrated a greater than additive effect when combined with accelerated fractionated radiation in this human tumour model. Cisplatin appears to be especially beneficial as a radiation enhancer when given throughout the course of radiation. Received: 15 December 1996 / Accepted: 25 March 1997     

Oliguric and non-oliguric acute renal failure in malaria in west zone of rajasthan,India-A comparative study

ObjectiveTo report a comparative clinical and histopathological study on oliguric and non-oliguric acute renal failure (ARF) in malaria.Method311 consecutive cases of malaria out of which 74 (23.79%) had ARF as per WHO criteria were conducted. Mean age was 32.58 (range 15–60 years) and male: female was 2:1.ResultMost of the cases developed ARF within 10 d of onset. 18 cases (11 falciparum, 2 mixed, 5 vivax) presented with oliguric and 56 (41 falciparum, 6 mixed, 9 vivax) with non-oliguric renal failure. Associated major manifestations were jaundice (75.68%), cerebral malaria (41.89%), bleeding manifestations (32.43%), severe anemia (27.03%), hypotension (25.68%), multi-organ failure (18.92%), severe thrombocytopenia (12.16%), and ARDS (8.11%). Kidney biopsy (n=20) showed acute tubular necrosis (n=7), Mesangioproliferative glomerulonephritis (n=4) or both (n=9). Hemodialysis was done in 8 cases of oliguric renal failure out of which 4 survived (average no. of session 2.9).ConclusionMost of the cases recovered within 3 weeks. Total mortality was 28.38% (n=21) and mortality was more in oliguric renal failure (72.22%) as compare to non-oliguric renal failure (14.29%).     

1 year follow Up results of “ARTIM HF TRIAL” (angiotensin receptor neprilysin inhibitor effect on TEI index & left ventricular mass in heart failure)

BackgroundSacubitril/Valsartan (ARNI) has now class 1 recommendation for treatment of heart failure with reduced ejection fraction (HFrEF). It has been shown to reduce cardiovascular morbidity & mortality in Heart failure with reduced ejection fraction (HFrEF) and significant improvement in all echocardiographic parameters besides TEI index. Tei index is a marker of inflammation, myocardial cell metabolism and its contractile function has not been evaluated as a distinctive entity so we took up this study to evaluate the effects of ARNI on the LV functions using two dimensional (2D)ECHO parameters in Indian population and to assess TEI index for myocardial function.Methods256 patients with class II, III or IV HF and EF<40% were enrolled. 171(66.8%) were males and 85(33.2%) were females. Patients were evaluated at baseline, 6 and 12 months for LVEF, LV mass &,LVMPI. Drug was discontinued in 2 patients due to angioedema, in 5 patients due to acute kidney injury and in 2 patients due to hypotension. LV mass measurement done by linear echocardiographic method and Flow Doppler method used for TEI index calculation.ResultsBaseline parameters in 247 patients were mean EF = 26.33 ± 6.28%, mean LV mass = 270.84 ± 68.94 gm, mean Tei Index = 0.852 ± 0.22. ARNI use was associated with an average gradual increase in EF, from a mean baseline of 26.33 ± 6.28% to 33.88 ± 7.73%(p = 0.000001) after 1 year of treatment. There was a significant progressive reduction of 57.97 g/m2 in mean LV mass index after 1 year of treatment (p = 0.000001).TEI index showed significant reduction from baseline mean 0.85 ± 0.22 to 0.70 ± 0.12(p = 0.000001)after 1 year of treatment.ConclusionUse of ARNI as additive adjunct to standard care of treatment resulted in significant progressive decline in LV mass and increase in TEI index.     

Evaluation of Factors in Relation with the Non-Compliance to Curative Intent Radiotherapy among Patients of Head and Neck Carcinoma: A Study from the Kumaon Region of India

Introduction:

Radiotherapy (RT)-based curative regimens for head and neck squamous cell carcinomas (HNSCC) deliver a dose of 66–70 Gray (Gy) over a period of 6–7 weeks, and incomplete treatments are unlikely to result in cure. Non-compliance to RT is major contributory factor to treatment failure.

Aims:

To assess the proportion of patients who do not complete planned treatment after initiation of curative RT. This study also aims to explore a possible relationship of non-compliance due to socio-economic, disease-related and treatment-related factors.

Materials and Methods:

The records of HNSCC patients treated from January 2012–December 2013 were audited. Data from the treatment records were to collect patient-related, disease-related, and social demographic parameters. Of the patients who had not completed treatment, the reasons behind the same were investigated.

Results:

Of the 324 patients of HNSCC who were initiated on radical RT, a total of 76 patients were found to have discontinued treatment without authorization of the treating clinician. There was no significant predilection for treatment non-compliance with regards to patient age, educational status, religion, site of the disease, use of neoadjuvant chemotherapy, or use of concurrent chemotherapy. There tended to be a higher association of treatment non-compliance among patients residing >100 km away from the treatment center, patients hailing from hilly regions, patients without the below poverty line (BPL) card, unemployed patients, and patients with stage IV-A/B disease. Of the 76 patients who did not complete treatment, telephonic questionnaire could be obtained from 54 patients. Causes for non-compliance included preference for traditional healers (22.2%), fear of toxicity (7.4%), logistic reasons (18.5%), financial reasons (24.1%), and lack of interest/faith in RT (5.6%).

Conclusion:

There is a high incidence of treatment default among patients of HNSCC during RT in this region. The revelation of the higher propensity for treatment default among patients from distant, hilly regions, unemployed, patients without BPL cards, and stages-IVA/IVB highlights the need for specific interventions for these special populations.     

Space radiation-induced inhibition of neurogenesis in the hippocampal dentate gyrus and memory impairment in mice: ameliorative potential of the melatonin metabolite, AFMK

Evaluation of potential health effects from high energy charged particle radiation exposure during long duration space travel is important for the future of manned missions. Cognitive health of an organism is considered to be maintained by the capacity of hippocampal precursors to proliferate and differentiate. Environmental stressors including irradiation have been shown to inhibit neurogenesis and are associated with the onset of cognitive impairments. The present study reports on the protective effects of N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK), a melatonin metabolite, against high energy charged particle radiation-induced oxidative damage to the brain. We observed that radiation exposure (2.0 Gy of 500 MeV/nucleon (56)Fe beams, a ground-based model of space radiation) impaired the spatial memory of mice at later intervals without affecting the motor activities. AFMK pretreatment significantly ameliorated these neurobehavioral ailments. Radiation-induced changes in the population of immature and proliferating neurons in the dentate gyrus were localized using anti-doublecortin (Dcx) and anti-Ki-67 expression. AFMK pretreatment significantly inhibited the loss of Dcx and Ki-67 positive cells. Moreover, AFMK pretreatment ameliorated the radiation-induced augmentation of protein carbonyls and 4-hydroxyalkenal + malondialdehyde (MDA + HAE) in the brain and maintained the total antioxidant capacity of plasma and nonprotein sulfhydryl contents in brain.